2. Introduction – Breast Cancer

 

The main rationale for updating the guideline is the consistently high epidemiological importance of breast cancer and the associated burden of disease. In this context, the effects of new care concepts in their implementation must be examined. The need to update the guideline also arises from the existence of new scientific findings and the further development of the guideline methodology. In addition, an editorial and content review and revision of the core statements and recommendations of the guideline is required at regular intervals. The objectives of the S3 guideline for the early detection, diagnosis, therapy and aftercare of breast cancer were retained from the original version and the first two updates and supplemented or specified for the third new edition:

• Consideration of current findings of evidence-based medicine and recognised treatment concepts
• consideration of the findings from disseminated guidelines and the comprehensive coverage of guideline-based quality indicators in the updating and implementation of the guideline
• Supporting the involvement of patients in therapy decisions and positioning their individual needs
• Comprehensive implementation of multidisciplinary, quality-assured and cross-sectoral care for breast cancer
• concrete efforts to improve the provision of needs-based and quality-assured psychosocial care and rehabilitation
• Support of the documentation of epidemiology and progression of breast cancer diseases by clinical cancer registers
• systematic consideration of the recommendations of initial, continuing and further training and in quality management systems
• systematic consideration of the recommendations and quality indicators derived from them in disease management programmes (DMPs), certification procedures of breast centres, cancer registries and external comparative quality assurance and standardisation of documentation requirements.

Improving the knowledge of the disease among non-affected persons and patients is an important goal for which there is a clear potential for improvement. It is a prerequisite for empowering women to participate in therapy decisions. At present, information is increasingly being made available on the Internet, but in many cases with very varying, sometimes unacceptable quality. Particularly in the area of breast cancer, a flood of information and educational material is available, the quality of which is predominantly assessed as poor. Within the framework of the OL-program, different versions of the patient guideline have been created, which are regularly adapted after the corresponding updates. The respective valid versions of the Women's and Patient Guidelines are available free of charge (see Chapter 1.9).

Addressees:
The recommendations of the interdisciplinary guideline (LL) are addressed to all physicians and members of professional groups involved in the care of citizens in the context of early detection and patients with breast cancer (gynaecologists, general practitioners, radiologists, pathologists, radio-oncologists, haemato-oncologists, psycho-oncologists, physiotherapists, nursing staff, etc.) and all women with breast cancer and their relatives.

Other indirect addressees are:

• medical and scientific societies and professional associations
• Representation of the interests of women (women's health organisations, patient and self-help organisations)
• Quality assurance institutions and projects at federal and state level
• health policy institutions and decision-makers at federal and state level
• those responsible for DMP programmes and integrated care contracts
• Cost unit
• as well as the public for information on good medical practice.

 

To classify the risk of bias in the identified studies, this guideline uses the system of the Oxford Centre for Evidence-based Medicine in the 2009 version, as shown in Table 5. This system provides for the classification of studies for different clinical questions (benefit of therapy, prognostic significance, diagnostic value).

Scheme of evidence grading according to Oxford (version March 2009)

Level	Therapy / Prevention, Aetiology / Harm	Prognosis	Diagnosis	Differential diagnosis / symptom prevalence study	Economic and decision analyses
1a	SR (with homogeneity) of RCTs	SR (with homogeneity) inception cohort studies; CDR validated in different populations	SR (with homogeneity) of Level 1 diagnostic studies; CDR with 1b studies from different clinical centers	SR (with homogeneity) of prospective cohort studies	SR (with homogeneity) of Level 1economic studies
1b	Individual RCT (with narrow Confidence Interval)	Individual inception cohort study with > 80% follow-up; CDR validated in a single population	Validating cohort study with good reference standards; or CDR tested within one clinical centre	Prospective cohort study with good follow-up	Analysis based on clinically sensitive costs or alternatives; systematic review(s) of the evidence; and including multi-way sensitivity analyses
2a	SR (with homogeneity) of cohort studies	SR (with homogeneity) of either retrospective cohort studies or untreated control groups in RCTs	SR (with homogeneity) of Level >2 diagnostic studies	SR (with homogeneity) of Level 2b and better studies	SR (with homogeneity) of Level >2 economic studies
2b	Individual cohort study (including low quality RCT; e.g, <80% follow-up)	Retrospective cohort study or follow-up of untreated control patients in an RCT; Derivation of CDR or validated on split-sample only	Exploratory cohort study with good reference standards; CDR after derivation, or validated only on split-sample or databases	Retrospective cohort study, or poor follow-up	Analysis based on clinically sensitive costs or alternatives; limited review(s) of the evidence, or single studies; and including multi-way sensitivity analyses
2c	"Outcomes" Research; Ecological studies	"Outcomes" Research		Ecological studies	Audit or outcomes research
3a	SR (with homogeneity) of case-control studies		SR (with homogeneity) of 3b and better studies	SR (with homogeneity) of 3b and better studies	SR (with homogeneity) of 3b and better studies
3b	Individual Case Control Study		Non-consecutive study; or without consistently applied reference standards	Non-consecutive cohort study; or very limited population	Analysis based on limited alternatives or costs, poor quality estimates of data, but including sensitivity analyses incorporating clinically sensitive variations
4	Case-series (and poor quality cohort and case-control studies)	Case series (and poor quality prognostic cohort studies)	Case control study, poor or non-independent reference standard	Case-series or superseded reference standards	Analysis with no sensitivity analysis
5	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles

 

The German Cancer Aid provided the financial means through the Oncology Guidelines Programme (OL). These funds were used for personnel costs, office material, literature procurement and the consensus conferences (room rent, technology, catering, moderator fees and travel expenses of the participants). The guideline was developed with editorial independence from the financing organization. During the guideline process, all members submitted a written declaration of any existing conflicts of interest.

Obtaining declarations of conflict of interest

From March 2016 onwards, declarations of conflict of interest were obtained from all persons involved using the updated AWMF form (see Guidelines Report), with step-by-step indication of the level of remuneration and explicit request for intellectual (academic) conflicts of interest (schools, publication activity, etc.). The completeness of the declarations was achieved in October 2016. Including methodologists, individual experts and deputies of mandate holders of the professional societies, the guideline group comprises about 90 persons.

Assessment of conflicts of interest

In the form used, those who had to fill in the form were asked to indicate whether there was a thematic link with the present guideline topic. However, a final self-assessment of whether a conflict of interest exists was no longer carried out. The conflict of interest declarations were evaluated by a working group nominated by the steering group. The working group consisted of Prof. Dr. R. Kreienberg (Senior Coordinator, Gynaecologist, former Director of the University Women's Hospital Ulm, DGGG), Prof. Dr. U.S. Albert (Senologist, DGS), Prof. Dr. W. Budach (Director of the Clinic for Radiotherapy of the University Hospital in Düsseldorf, DEGRO) and Dr. M. Nothacker, MPH (Methodologist, AMWF). All results were presented to an external consultant (Prof. Dr. Ludwig of the AKDÄ) and confirmed.

Evaluation criteria

The initial assessment of the declarations of conflict of interest was carried out by all evaluators for all persons, completely independently of the other evaluators, according to the classification: 0 = none, 1 = low, 2 = moderate, 3 = serious in terms of the assessed level of conflict of interest. Reasons for this were recorded. The assessments of the working group members were combined and the range of the assessments was determined. In a joint telephone conference, the assessments were discussed which had at least a 2 (moderate conflict of interest n=31) and/or a 3 (serious conflict of interest, n=15). After discussion, the final ranking was determined. The following criteria were examined with regard to the existing thematic reference and the absolute level of remuneration and the strength of the relationship:

1. Lectures financed by the industry
2. Review/Advisory Board: Paid review/advisory work for industrial companies (Scientific Advisory Board: work for industry)
3. Third-party funds directly financed by industry

With only a few presentations, the evaluation was "1 - low". In the case of the existence of relevant expert opinions/consultancy or activities in a scientific field, the assessment was "1 - low". In the case of relevant activities as an assessor/consultant or in a scientific advisory board and/or receipt of third-party funding from industry, the assessment was either "2 - moderate" or "3 - serious". The ratings were assigned by consensus in the overall view of the information and are subject to

© Oncology guideline programme | S3 guideline breast cancer| Version 4.1 | September 2018

2.2 Methodological principles 34

a subjective assessment, as the information provided in the conflict of interest forms did not consistently allow for a reliable quantitative assessment and there was no rationale for a fixed cut-off.

Finally, the evaluations were assigned as follows:

44 times = assessment 2 - 14 elected officials and 30 experts were affected 0 times = assessment 3

Dealing with conflicts of interest

The following approach was implemented:

• 0 -1 (no or minor conflict of interest): no special measures.
• 2 (moderate conflict of interest): double vote on the topics concerned (additional calculation of the result of the vote if persons with a moderate conflict of interest are excluded).
• 3 (serious conflict of interest): no vote on the topics concerned, review of the chapter by third parties is obligatory, optional exclusion from the discussion (review should be carried out by methodologists or members of the guideline group who are not biased with regard to content).

The issues potentially affected by conflicts of interest were identified on the basis of the substances listed.

Guidance coordinators and members of the steering group were excluded from the vote as a matter of principle. In order to create an empirical basis for the actual risk of bias in relation to the overall group assessment, the persons with moderate conflicts of interest were identified by means of a preceding question before the electronic voting process. Subsequently, this blinded grouping made it possible to conduct sensitivity analyses with regard to the group of persons with a moderate conflict of interest (result if all persons with a conflict of interest were involved vs.)

This procedure was discussed at the end of November with an independent expert and expert on conflicts of interest, Prof. Dr. Ludwig of the AKDÄ, who confirmed that the procedure was appropriate.

At this point we would like to thank all employees for their exclusively voluntary work on the project.